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The impact of sub-cellular location and intracellular neuronal proteins on properties of GABA(A) receptors

Birnir, Bryndis LU and Korpi, Esa R (2007) In Current Pharmaceutical Design 13(31). p.3169-3177
Abstract
Most studies of GABA(A) receptor accessory proteins have focused on trafficking, clustering and phosphorylation state of the channel-forming subunits and as a result a number of proteins and mechanisms have been identified that can influence the GABA(A) channel expression and function in the cell plasma membrane. In the light of a growing list of intracellular and transmembrane neuronal proteins shown to affect the fate, function and pharmacology of the GABA(A) receptors in neurons, the concept of what constitutes the native GABA(A) receptor complex may need to be re-examined. It is perhaps more appropriate to consider the associated proteins or some of them to be parts of the receptor channel complex in the capacity of ancillary proteins.... (More)
Most studies of GABA(A) receptor accessory proteins have focused on trafficking, clustering and phosphorylation state of the channel-forming subunits and as a result a number of proteins and mechanisms have been identified that can influence the GABA(A) channel expression and function in the cell plasma membrane. In the light of a growing list of intracellular and transmembrane neuronal proteins shown to affect the fate, function and pharmacology of the GABA(A) receptors in neurons, the concept of what constitutes the native GABA(A) receptor complex may need to be re-examined. It is perhaps more appropriate to consider the associated proteins or some of them to be parts of the receptor channel complex in the capacity of ancillary proteins. Here we highlight some of the effects the intracellular environment has on the GABA-activated channel function and pharmacology. The studies demonstrate the need for co-expression of accessory proteins with the GABA(A) channel-forming subunits in heterologous expression systems in order to obtain the full repertoire of GABA(A) receptors characteristics recorded in the native neuronal environment. Further studies e.g. on gene-modified animal models are needed for most of the accessory proteins to establish their significance in normal physiology and in pathophysiology of neurological and psychiatric diseases. The challenge remains to elucidate the effects that the accessory proteins and processes (e.g. phosphorylation) plus the sub-cellular location have on the "fine-tuning" of the functional and pharmacological properties of the GABA(A) receptor channels. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
four transmembrane regions, conductance, GABA binding site, neurodegeneration, synaptic receptors
in
Current Pharmaceutical Design
volume
13
issue
31
pages
3169 - 3177
publisher
Bentham Science Publishers
external identifiers
  • pmid:18045166
  • wos:000253583400002
  • scopus:36749096756
ISSN
1381-6128
DOI
10.2174/138161207782341330
language
English
LU publication?
yes
id
0b23f2de-9f86-40b8-b367-e505c0416ce3 (old id 1140887)
date added to LUP
2008-08-14 11:47:40
date last changed
2017-01-01 07:31:57
@article{0b23f2de-9f86-40b8-b367-e505c0416ce3,
  abstract     = {Most studies of GABA(A) receptor accessory proteins have focused on trafficking, clustering and phosphorylation state of the channel-forming subunits and as a result a number of proteins and mechanisms have been identified that can influence the GABA(A) channel expression and function in the cell plasma membrane. In the light of a growing list of intracellular and transmembrane neuronal proteins shown to affect the fate, function and pharmacology of the GABA(A) receptors in neurons, the concept of what constitutes the native GABA(A) receptor complex may need to be re-examined. It is perhaps more appropriate to consider the associated proteins or some of them to be parts of the receptor channel complex in the capacity of ancillary proteins. Here we highlight some of the effects the intracellular environment has on the GABA-activated channel function and pharmacology. The studies demonstrate the need for co-expression of accessory proteins with the GABA(A) channel-forming subunits in heterologous expression systems in order to obtain the full repertoire of GABA(A) receptors characteristics recorded in the native neuronal environment. Further studies e.g. on gene-modified animal models are needed for most of the accessory proteins to establish their significance in normal physiology and in pathophysiology of neurological and psychiatric diseases. The challenge remains to elucidate the effects that the accessory proteins and processes (e.g. phosphorylation) plus the sub-cellular location have on the "fine-tuning" of the functional and pharmacological properties of the GABA(A) receptor channels.},
  author       = {Birnir, Bryndis and Korpi, Esa R},
  issn         = {1381-6128},
  keyword      = {four transmembrane regions,conductance,GABA binding site,neurodegeneration,synaptic receptors},
  language     = {eng},
  number       = {31},
  pages        = {3169--3177},
  publisher    = {Bentham Science Publishers},
  series       = {Current Pharmaceutical Design},
  title        = {The impact of sub-cellular location and intracellular neuronal proteins on properties of GABA(A) receptors},
  url          = {http://dx.doi.org/10.2174/138161207782341330},
  volume       = {13},
  year         = {2007},
}